1. Field of the Invention
The present invention relates generally to methods and compositions which are effective in increasing or enhancing the cytotoxic effectiveness of human natural killer cells. More particularly, the present invention relates to the discovery and purification of a protein from red blood cell cytosol which is an effective factor that enhances the activity of natural killer cells.
2. Description of Related Art
The publications and other reference material referred to herein to describe the background and the detailed description of the invention and to provide additional detail regarding its practice are hereby incorporated by reference. For convenience, the referenced materials are numerically referenced and grouped in the appended bibliography.
Natural killer (NK) cells are a subset of lymphocytes found in blood and lymphoid tissues and especially the spleen. NK cells are derived from bone marrow and appear as large lymphocytes with prominent cytoplasmic granules. They are sometimes referred to as large granular lymphocytes. NK cells are believed to be responsible for natural surveillance against tumor growth and metastasis and are important regulators for hematopoiesis, including erythropoiesis (1-3).
The activity of NK cells has been shown to increase when several different protein products are present. These protein products include interferons, IL-1, IL-2, IL-6, several types of interferon and tumor necrosis factor-.alpha. (4-7). In addition, a B cell product termed NK stimulating factor (NKSF) (12) or cytotoxic lymphocyte maturation factor (13), has been reported as another activator of NK cells. All of these proteins have been purified, identified and cloned.
It has also been demonstrated that NK cells express higher cytotoxic activity against tumor cells in the presence of red blood cells (RBC) (8). Red blood cells are the major cellular component of the peripheral blood and occupy up to one-half of the total blood volume. Therefore, NK cells are usually in constant contact with RBC in the blood and, in fact, have a specific receptor, CD2, that facilitates interactions with RBC (9, 10).
The mechanism by which red blood cells enhance NK cell activity is not entirely known. For example, it has not been established whether the red blood cell itself is responsible for enhancing cytotoxicity or if one or more cellular products are responsible. Accordingly, there is a present need to establish the mechanism by which red blood cells enhance NK cell activity. Further, it would be desirable to isolate and identify any specific cellular components or cellular products which cause the observed NK cell enhancement. Such components or factors could then be used together with or apart from the red blood cell to enhance NK cell activity.